Evidence map›Paper›PMID 33963284›Full record

ReviewMolecular psychiatry2022

Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor.

Yan Wei, Lijia Chang, Kenji Hashimoto

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 6 pooled it
12.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

120 citing papers in PubMed, 6 syntheses or guidelines pooled it, 229 citations in OpenAlex.

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60 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Yan WeiDivision of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.ORCID http://orcid.org/0000-0002-2682-3780
Lijia ChangDivision of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
Kenji HashimotoDivision of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. hashimoto@faculty.chiba-u.jp.ORCID http://orcid.org/0000-0002-8892-0439
Center for Forensic Mental Health, Chiba University · JPSouthwest Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The discovery of robust antidepressant actions exerted by the N-methyl-D-aspartate receptor (NMDAR) antagonist (R,S)-ketamine has been a crucial breakthrough in mood disorder research. (R,S)-ketamine is a racemic mixture of equal amounts of (R)-ketamine (arketamine) and (S)-ketamine (esketamine). In 2019, an esketamine nasal spray from Johnson & Johnson was approved in the United States of America and Europe for treatment-resistant depression. However, an increasing number of preclinical studies show that arketamine has greater potency and longer-lasting antidepressant-like effects than esketamine in rodents, despite the lower binding affinity of arketamine for the NMDAR. In clinical trials, non-ketamine NMDAR-related compounds did not exhibit ketamine-like robust antidepressant actions in patients with depression, despite these compounds showing antidepressant-like effects in rodents. Thus, the rodent data do not necessarily translate to humans due to the complexity of human psychiatric disorders. Collectively, the available studies indicate that it is unlikely that NMDAR plays a major role in the antidepressant action of (R,S)-ketamine and its enantiomers, although the precise molecular mechanisms underlying antidepressant actions of (R,S)-ketamine and its enantiomers remain unclear. In this paper, we review recent findings on the molecular mechanisms underlying the antidepressant actions of (R,S)-ketamine and its potent enantiomer arketamine. Furthermore, we discuss the possible role of the brain-gut-microbiota axis and brain-spleen axis in stress-related psychiatric disorders and in the antidepressant-like action of arketamine. Finally, we discuss the potential of arketamine as a treatment for cognitive impairment in psychiatric disorders, Parkinson's disease, osteoporosis, inflammatory bowel diseases, and stroke.

Indexed as

Depressive Disorder, Treatment-ResistantKetamineAntidepressive AgentsDepressionHumansReceptors, N-Methyl-D-AspartateAntidepressive AgentsKetamineReceptors, N-Methyl-D-Aspartate

Identifiers

PMID33963284
PMCPMC8960399
OpenAlexW3158143766

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.